Movements abnormal gene contains trinucleotide repeat expansion. Medical search. Frequent questions

Huntington's disease (HD) is the most prevalent autosomal dominant, trinucleotide repeat neurodegenerative disease. (grantome.com)
Huntington's disease (HD) is an autosomal dominant neurodegenerative condition associated with abnormal movements, cognitive deterioration, and psychiatric symptoms. (bmj.com)
Huntington disease (HD) is a genetic, autosomal dominant, neurodegenerative disorder characterized clinically by disorders of movement, progressive dementia, and psychiatric and/or behavioral disturbance. (medscape.com)

It is caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin ( HTT ) gene on chromosome 4, which is responsible for the expression of the protein huntingtin ( Nance, 2017 ). (frontiersin.org)

The huntingtin gene encodes a protein of 350 kD;the disease causing mutation is an expansion of an amino-terminal polyglutamine repeat of more than 36 successive glutamines. (grantome.com)
When translated into protein the CAG repeat encodes for a polyglutamine stretch in the disease-causing proteins. (biologie-uni-siegen.de)
The lilli gene encodes a nuclear protein related to the AF4/FMR2 family. (sdbonline.org)
The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase. (lookformedical.com)
These guarantee onset of early-onset familial Alzheimer disease and all occur in the region of the APP gene that encodes the Aβ domain. (findzebra.com)

Hundreds of different variants (also called mutations) in the AR gene have been identified in people with androgen insensitivity syndrome, a condition that affects sexual development before birth and during puberty. (medlineplus.gov)
We were interested to test if wild type huntingtin protected against the toxicity of polyglutamine expansion mutations. (bmj.com)
The decision to rescreen a patient should be undertaken only with the guidance of a genetics professional who can best assess the incremental benefit of repeat testing for additional mutations. (acog.org)
In humans, mutations affecting the genes of this family are associated with specific diseases. (sdbonline.org)
We hypothesize that there might be at least three types of autism susceptibility genes/mutations that can be (i) specific to an individual patient or family, (ii) in a genetically isolated sub-population and (iii) a common factor shared amongst different populations. (neurotransmitter.net)
The genes/mutations could act alone or interact with other genetic and/or epigenetic or environmental factors, causing autism or related disorders. (neurotransmitter.net)
21 allelic mutations have been discovered in the APP gene. (findzebra.com)

Nucleotide excision repair proteins are mobilized to this area where one likely outcome is the expansion of nucleotides in the template strand while the other is the absence of nucleotides. (wikipedia.org)
If these repeats are found in coding regions then the variations to the polynucleotide sequence can result in the formation of abnormal proteins in eukaryotes. (wikipedia.org)
The abnormal mRNA has been found in clumps of proteins and mRNA (intranuclear inclusions) that are found in brain and nerve cells in people with FXTAS. (medlineplus.gov)
In our studies we have identified a set of proteins that aberrantly bind to mutant CAG repeats. (biologie-uni-siegen.de)
This abnormal binding can lead to both: a loss of physiological function of the RNA-binding proteins and a gain of function of these proteins at the mutant CAG repeat RNA. (biologie-uni-siegen.de)
In animal models, FAN1 prevents somatic expansion of CAG triplet repeats, whereas MMR proteins promote this process. (bvsalud.org)
The abnormal aggregation and accumulation of specific proteins in the form of cytoplasmic inclusion is common pathological feature of most age-related neurodegenerative diseases, such as Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD) and amyotrophic lateral sclerosis (ALS). (en-journal.org)

Huntington disease (HD) is associated with an excessive sequence of CAG repeats in the 5' end of HTT (alias IT15- interesting transcript number 15), a 350-kD gene located on the short arm of chromosome 4. (medscape.com)
Etiology HCHWA-D is due to a mutation in the APP gene on chromosome 21q21.2, encoding the beta-amyloid precursor protein. (findzebra.com)

Co-transcriptional formation of stable RNA·DNA hybrids can also enhance the instability of repeat tracts. (bvsalud.org)
These results suggest that transcriptional elongation control is especially important for rapidly expressed genes to support digestion and metabolism, many of which have sex-biased function. (sdbonline.org)

One of the most common causes of genetic neurodegeneration is expansion of short repetitive DNA sequences, for example CAG trinucleotide repeats. (biologie-uni-siegen.de)
The Alzheimer-Dementia Panel examines 16 genes associated with an increased risk of developing neurodegenerative conditions: Alzheimer's disease and genetic disorders that cause dementia. (tesiscolorado.com)
Carrier screening is a term used to describe genetic testing that is performed on an individual who does not have any overt phenotype for a genetic disorder but may have one variant allele within a gene(s) associated with a diagnosis. (acog.org)
Genetic testing revealed 43 CAG repeats in the HD gene. (medscape.com)
The first stage involved identifying, in unrelated subjects showing linkage to 2q24-q33, genetic variants in exons and flanking sequence within candidate genes and comparing the frequency of the variants between autistic and unrelated nonautistic subjects. (neurotransmitter.net)

Patients with Huntington's disease (HD) develop cognitive deficits, depression and movement abnormalities. (grantome.com)

Huntington disease is normally progressive and results in movement, cognitive and psychiatric disorders. (wikipedia.org)
The so-called CAG repeat diseases are characterized by symptoms such as the progressive loss of cognitive abilities and progressive movement disorders. (biologie-uni-siegen.de)
Clinically, the disease is characterized by complex and variable symptoms that include movement disorders, psychiatric problems and cognitive decline 2 . (nature.com)
Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused by expansion of polyglutamine (polyQ) repeat in exon 1 of huntingtin (HTT). (en-journal.org)

Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. (nature.com)
Huntington's disease (HD) is a fatal neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the Huntingtin gene. (bvsalud.org)

In all cases, age at onset correlates inversely with repeat number. (bmj.com)
In order to identify genes that may modify disease onset and progression, genome-wide association and gene expression studies have been performed 12 , 13 . (nature.com)
Human genome-wide association studies have identified FAN1 and several DNA mismatch repair (MMR) genes as modifiers of Huntington's disease age of onset. (bvsalud.org)
These results provide a mechanistic basis for the role of FAN1 in preventing repeat expansion and could explain the antagonistic effects of MMR and FAN1 in disease onset/progression. (bvsalud.org)

These include spinal and bulbar muscular atrophy ( trinucleotide expansion in the AR gene), dentatorubral-pallidoluysian atrophy ( trinucleotide expansion in the DRPLA gene), spinocerebellar ataxia type 1 ( trinucleotide expansion in the SCA1gene), Machado-Joseph disease ( trinucleotide expansion in the SCA3 gene), myotonic dystrophy ( trinucleotide expansion in the DMPK gene), and Friedreich's ataxia ( a trinuncleotide expansion in the X25 gene). (wikipedia.org)
HD is a member of a family of neurodegenerative diseases caused by CAG/polyglutamine expansions, which include spinobulbar muscular atrophy (SBMA), spinocerebellar ataxias (SCA) types 1, 2, 3, 6, and 7, and dentatorubral-pallidoluysian atrophy. (bmj.com)
This test is not a gene panel for all types of spinocerebellar ataxia (SCA). (mayocliniclabs.com)
order SCAP / Spinocerebellar Ataxia Repeat Expansion Panel, Varies. (mayocliniclabs.com)

For unknown reasons, the premutation leads to the overproduction of abnormal FMR1 mRNA that contains the repeat expansion. (medlineplus.gov)
Researchers believe that the abnormal mRNA causes the signs and symptoms of FXPOI. (medlineplus.gov)
As in FXPOI (described above), the premutation causes overproduction of abnormal FMR1 mRNA containing the expanded repeat region, and researchers believe that this abnormal mRNA causes FXTAS. (medlineplus.gov)
Innovations include targeting mRNA alleles for RNAi, use of HD mouse models that express only human huntingtin genes, quantitative measurement of huntingtin allelic mRNA based on SNP heterozygosities, deep sequencing analysis to identify 3 UTR huntingtin mRNA regulation, and zinc finger nuclease strategy to eliminate huntingtin alleles at the genomic level. (grantome.com)
2019. Effect of trinucleotide repeat expansion on the expression of TCF4 mRNA in Fuchs' endothelial corneal dystrophy . (cardiff.ac.uk)

Many human diseases have been reported to be associated with trinucleotide repeat expansions including Huntington's disease. (wikipedia.org)
An individual who is not affected by Huntington's disease will have 6-35 tandem repeats at the HD locus. (wikipedia.org)
The expansion of the HD locus results in a dysfunctional protein leading to Huntington's disease. (wikipedia.org)
The goal of our research is to develop a novel eye-movement technique to aid the diagnosis and progression monitoring of Huntington's disease (HD). (hdsa.org)
Huntington's disease (HD) is caused by expansion of polyglutamine repeats in the protein huntingtin, which affects the corpus striatum of the brain. (encyclopedia.pub)

The Parkinson's Disease Comprehensive Panel examines 26 genes associated with an increased risk of developing the neurodegenerative condition Parkinson's Disease. (tesiscolorado.com)

We will examine how gene silencing can reduce production of the mutant huntingtin protein that causes HD, thereby preventing dysfunction and death in neurons in animal models of HD and in HD neurons in culture. (grantome.com)
The causative mutation is a (CAG) n trinucleotide repeat expansion of more than 35 repeats, which is translated into an abnormally long polyglutamine tract in the huntingtin protein. (bmj.com)
Possibly, the abnormal huntingtin protein undergoes proteolysis and is then transported to the nucleus, where it undergoes aggregation. (medscape.com)

HD supposedly can cause psychiatric disorders in 2 ways: (1) by the direct action of the gene on striatal neurons, and (2) by the indirect effect of the disordered family environment on the children, regardless of whether they inherited the HD gene. (medscape.com)

METHOD: Mutation screening of positional candidate genes was performed in two stages. (neurotransmitter.net)
Next-generation sequencing of the whole exome is useful for testing for multiple candidate genes simultaneously or for discovering new, rare disorders. (medlink.com)

This CAG segment is called a triplet or trinucleotide repeat. (medlineplus.gov)
To understand the molecular basis of these opposing effects, we evaluated FAN1 nuclease function on DNA extrahelical extrusions that represent key intermediates in triplet repeat expansion. (bvsalud.org)
Activation of FAN1 in this manner results in DNA cleavage in the vicinity of triplet repeat extrahelical extrusions thereby leading to their removal in human cell extracts. (bvsalud.org)

A slippage event normally occurs when a sequence of repetitive nucleotides (tandem repeats) are found at the site of replication. (wikipedia.org)
Tandem repeats are unstable regions of the genome where frequent insertions and deletions of nucleotides can take place, resulting in genome rearrangements. (wikipedia.org)
One region of the FMR1 gene contains a particular DNA segment known as a CGG trinucleotide repeat, so called because this segment of three DNA building blocks (nucleotides) is repeated multiple times within the gene. (medlineplus.gov)

trinucleotides or hexanucleotides), alterations in most regulatory regions (promoter regions) or deep intronic regions (greater than 20bp from an exon). (tesiscolorado.com)
METHODS We cotransfected neuronal (SK-N-SH, human neuroblastoma) and non-neuronal (COS-7, monkey kidney) cell lines with HD exon 1 (containing either 21 or 72 CAG repeats) construct DNA and either full length wild type huntingtin or pFLAG (control vector). (bmj.com)
RESULTS Full length wild type huntingtin significantly reduced cell death resulting from the mutant HD exon 1 fragments containing 72 CAG repeats in both cell lines. (bmj.com)
Wild type huntingtin did not significantly modulate cell death caused by transfection of HD exon 1 fragments containing 21 CAG repeats in either cell line. (bmj.com)
35) in the first exon of the huntingtin ( HTT , IT15 ) gene 1 . (nature.com)

Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. (en-journal.org)

The FMR1 gene provides instructions for making a protein called FMRP. (medlineplus.gov)
A trinucleotide repeat expansion in the FMR1 gene increases a woman's risk of developing a condition called fragile X-associated primary ovarian insufficiency (FXPOI). (medlineplus.gov)
In this condition, the CGG trinucleotide repeat in the FMR1 gene is repeated about 55 to 200 times, which is referred to as a premutation. (medlineplus.gov)
In addition, the repeats make producing protein from the blueprint more difficult, and consequently, some people with the FMR1 gene premutation have lower than normal amounts of FMRP. (medlineplus.gov)
Men, and some women, with an FMR1 gene premutation are at increased risk of developing a disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). (medlineplus.gov)
Almost all cases of fragile X syndrome are caused by an expansion of the CGG trinucleotide repeat in the FMR1 gene. (medlineplus.gov)
Negative association findings and research involving the serotonin transporter gene, FMR1, RELN, WNT2, HOXA1, and HOXB1 genes may be found elsewhere on this site . (neurotransmitter.net)

It is a form of mutation that leads to either a trinucleotide or dinucleotide expansion, or sometimes contraction, during DNA replication. (wikipedia.org)
Although trinucleotide contraction is possible, trinucleotide expansion occurs more frequently. (wikipedia.org)
Are capable of sensing contraction and expansion of ECF volume. (abcmedicalnotes.com)

Researchers believe that a fragment of the androgen receptor protein containing the CAG repeats accumulates within these cells and interferes with normal cell functions. (medlineplus.gov)
Polyglutamine expansion =} Huntington accumulates in nucleus and cytoplasm =} cytoplasmic Huntington aggregates in axonal terminals, neuronal loss and gliosis. (neuroradiologycases.com)

In fact, we know that in people with other diseases that involve the striatum such as Parkinson's disease, these symptoms are related to abnormal reward signals in the striatum. (hdsa.org)

Within DNA trinucleotide repeat sequences, the repair of DNA damage by the processes of homologous recombination, non-homologous end joining, DNA mismatch repair or base excision repair may involve strand slippage mispairing leading to trinucleotide repeat expansion when the repair is completed. (wikipedia.org)
Genomic regions with a high proportion of repeated DNA sequences (tandem repeats, microsatellites) are prone to strand slippage during DNA replication and DNA repair. (wikipedia.org)
Specific uORFs are known to control protein expression by tuning translation rates of downstream protein-coding sequences, and potential uORFs have been identified in ~50% of all human protein-coding genes 1 , 2 . (nature.com)

Warning signs of these diseases include, but are not limited to abnormal imaging of the brain, difficultly moving or controlling one's movement, memory loss that interferes with daily life, changes in mood and personality, difficulty having a conversation or completing familiar tasks, and confusion with the time or place. (tesiscolorado.com)
The large number of genes and the diversity of processes involved in the progression of neurological diseases in general, and HD in specific, emphasizes the need for comprehensive approaches in additional to studies of individual genes 14 . (nature.com)
Neurodegenerative diseases (NDDs) are devastating disorders which impair memory, cognition, movements, and general functioning. (aao.org)

This assay will not detect certain types of genomic alterations which may cause disease such as, but not limited to, translocations or inversions, repeat expansions (eg. (tesiscolorado.com)
Translocations between MLL (a human trithorax -related gene) and AF4 or AF5q31 are involved in acute lymphoblastic leukemia (Wittwer, 2001, Tang, 2001 and Su, 2001). (sdbonline.org)

Because HD is an inherited disease, we expected that the mutant allele will differ from wild-type by at least a single nucleotide polymorphism, thereby offering a target for gene silencing by RNAi. (grantome.com)
Structurally, mutant CAG repeat RNA differs from the physiological RNA: the expanded CAG repeats fold into characteristic hairpin structures. (biologie-uni-siegen.de)
For example, we have identified a protein complex, which binds to and induces aberrant translation of mRNAs containing mutant CAG repeats. (biologie-uni-siegen.de)
2 The polyglutamine expansion mutation causes disease by conferring a novel deleterious function on the mutant protein and the severity correlates with increasing CAG repeat number and expression levels in transgenic mice and in cell culture models. (bmj.com)
These mutant phenotypes correlate with markedly reduced expression of the early zygotic genes serendipity alpha , fushi tarazu and huckebein , which are essential for cellularization and embryonic patterning (Tang, 2001). (sdbonline.org)
The polyglutamine repeats in mutant huntingtin cause its aggregation and elicit toxicity by affecting several cellular processes, which include dysregulated organellar stress responses. (encyclopedia.pub)

Although each of the CAG repeat expansion disorders is rare, together they represent one of the most common forms of inherited neurodegeneration. (biologie-uni-siegen.de)
Episodic ataxia type is characterized by attacks of gait ataxia, poor balance, nausea, vomiting, and sometimes particular eye movement disorders that is referred to as oscillopsia. (epilepsygenetics.net)
Whole exome sequencing is not suitable for detecting polynucleotide repeat disorders or large insertion/deletions. (medlink.com)

Additionally, testing for ATXN1 assesses for CAT ( cytosine-adenine-thymine ) trinucleotides that interrupt the CAG repeat tract. (mayocliniclabs.com)

Spinal and bulbar muscular atrophy, a disorder of specialized nerve cells that control muscle movement (motor neurons), results from an expansion of the CAG trinucleotide repeat in the AR gene. (medlineplus.gov)
Myotonic dystrophy type 1 is the most frequent form of muscular dystrophy in adults caused by an abnormal expansion of the CTG trinucleotide. (bvsalud.org)

MRI features of spinal cord infarction are central T2 hyperintensity without significant cord expansion or contrast enhancement. (abcmedicalnotes.com)

FXTAS is characterized by progressive problems with movement (ataxia), tremor, memory loss, reduced sensation in the lower extremities (peripheral neuropathy), and mental and behavioral changes. (medlineplus.gov)

Aim 1 examines in vivo in mice whether allele specific silencing can delay or prevent HD neuropathy and abnormal behaviors. (grantome.com)

For example, insertion of a single repeat unit in GAGAGA expands the sequence to GAGAGAGA, while insertion of two repeat units in [GA]6 would produce [GA]8. (wikipedia.org)
This CGG repeat segment is typically interrupted several times by a different three-base sequence, AGG. (medlineplus.gov)

In one region of the AR gene, a DNA segment known as CAG is repeated multiple times. (medlineplus.gov)

In long repeats, expansions may involve two or more units. (wikipedia.org)

In these cases, CGG is abnormally repeated more than 200 times, which makes this region of the gene unstable. (medlineplus.gov)

We will identify abnormal eye-movements that may indicate the presence and severity of HD. (hdsa.org)

Some variants lead to an abnormally short version of the androgen receptor protein, while others result in the production of an abnormal receptor that cannot bind to androgens or to DNA. (medlineplus.gov)

Genes showing reduced expression due to these RNAi treatments were short and enriched for genes encoding metabolic or enzymatic functions. (sdbonline.org)

Insertions are thought to be self-accelerating: as repeats grow longer, the probability of subsequent mispairing events increases. (wikipedia.org)

Almost half of the genes expressed in adults showed reduced expression, supporting a broad role for the three tested genes in steady-state transcript abundance. (sdbonline.org)

Other variants insert or delete multiple base pairs in the gene or affect how the gene is processed into a protein. (medlineplus.gov)
Using these variants, we map and validate gene-disease associations in two independent biobanks containing exome sequencing from 10,900 and 32,268 individuals, respectively, and elucidate their impact on protein expression in human cells. (nature.com)

Loss of FMR2 gene transcription causes mental retardation. (sdbonline.org)
The classic view of information processing in the cell by gene expression occurs through transcription followed by translation. (nature.com)

Ophthalmologic findings of AD include visual field deficits, decreased contrast sensitivity, impaired oculomotor function, and abnormal viewing behavior. (aao.org)

The variations change the number or order of DNA building blocks (base pairs) that make up the AR gene. (medlineplus.gov)
Researchers believe that AR gene variations may increase the activity of androgen receptors in the scalp. (medlineplus.gov)

This results in some repeats found in the template strand being replicated twice into the daughter strand. (wikipedia.org)
Therefore, replication slippage leads to a form of trinucleotide expansion which results in serious changes to protein structure. (wikipedia.org)
Our results suggest translation disrupting mechanisms relating uORF variation to reduced protein expression, and demonstrate that translation at uORFs is genetically constrained in 50% of human genes. (nature.com)
it results from expansion of polyglutamine repeats in the protein huntingtin [ 1 ] . (encyclopedia.pub)

The resulting androgen-receptor complex then binds to DNA and regulates the activity of androgen-responsive genes. (medlineplus.gov)

The HD gene is found in all human genomes. (wikipedia.org)
It allows users to obtain, visualize and prioritize molecular interaction networks using HD-relevant gene expression, phenotypic and other types of data obtained from human samples or model organisms. (nature.com)

It was originally known as a gene for familial ataxias and hemiplegic migraines with little connection to epilepsy, but its story has quickly changed. (epilepsygenetics.net)

Hundreds of genes were observed with sex-biased differential expression following treatment. (sdbonline.org)
2019. Convergent evidence that ZNF804A is a regulator of pre-messenger RNA processing and gene expression . (cardiff.ac.uk)
We showed previously that cytoplasmic release of mtDNA activates the cGAS STING TBK1 pathway resulting in interferon-stimulated gene (ISG) expression that promotes antiviral immunity4. (regenerativemedicine.net)
Here, we find that persistent mtDNA stress is not associated with basally activated NF-κB signalling or interferon gene expression typical of an acute antiviral response. (regenerativemedicine.net)

Patients identified with a disease-causing change (a pathogenic or likely pathogenic variant) in a gene on this panel have an increased risk of developing the associated neurodegenerative disease. (tesiscolorado.com)

Parkinson's Disease is characterized by progressive movement and balance issues. (tesiscolorado.com)

Instead of the typical 10 to 36 repeats, CAG is repeated from 38 to more than 60 times in people with this disorder. (medlineplus.gov)
Huntington Disease (HD) is a hereditary neurological disorder that shows a gene expansion associated with trinucleotide repeats. (medicalalgorithms.com)

This proposal addresses treatment of HD through study of basic mechanisms of silencing the gene that causes the disease. (grantome.com)

It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues. (lookformedical.com)

Anatomy1

Organisms2

Diseases19

Chemicals and Drugs16

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Psychiatry and Psychology2

Phenomena and Processes30

Information Science3

Health Care1

Autosomal dominant3

Cytosine-adenine-guanine1

Encodes5

Mutations7

Proteins7

Chromosome2

Transcriptional2

Genetic5

Abnormalities1

Cognitive4

Fatal neurodegenerative disorder caused2

Onset4

Spinocerebellar4

MRNA5

Huntington's5

Neurodegenerative condition1

Huntingtin protein3

Psychiatric1

Candidate genes2

Triplet3

Nucleotides3

Exon5

Protein aggregation1

FMR17

Contraction3

Accumulates2

Symptoms1

Sequences3

Diseases3

Translocations2

Mutant6

Disorders3

Tract1

Muscular2

Spinal1

Tremor1

Allele1

Sequence2

Segment known1

Involve1

Unstable1

Severity1

Abnormally1

RNAi1

Increases1

Adults1

Variants2

Transcription2

Findings1

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Results4

Regulates1

Human2

Familial1

Expression4

Pathogenic1

Parkinson's1

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Structurally1